The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

Patients with rosacea are more likely to experience ocular symptoms, including foreign body sensations, itching, dryness, hyperemia, and conjunctival telangiectasia, according to a study recently published in International Ophthalmology.

In the study, investigators compared the right eyes of 76 patients with acne rosacea and 113 age-matched and gender-matched patients without rosacea. The mean age of the patients was 47-48 years, and about 63% were females. Ophthalmologic examinations that included tear breakup time and optical CT-assisted infrared meibography were conducted, and participants were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire, which the authors say is widely used to assess aspects of ocular surface diseases.

National Rosacea Society

Compared with controls, significantly more patients with rosacea had itching (35.5% vs. 17.7%), dryness (46.1% vs. 10.6%), hyperemia (10.5% vs. 2.7%), conjunctival telangiectasia (26.3% vs. 1.8%), and meibomitis (52.6% vs. 31%) (P ≤ .05 for all), according to the investigators, from the departments of ophthalmology and dermatology, Dokuz Eylul University, Izmir, Turkey. The most common ocular symptom among those with rosacea was having a foreign body sensation (53.9% vs. 24.8%, P < .001).

Ocular surface problems were also more common among those with rosacea, and OSDI scores were significantly higher among those with rosacea, compared with controls.

Estee Williams, MD, a dermatologist in private practice in New York and assistant clinical professor of dermatology at Mount Sinai Hospital, also in New York, who was not involved with the study, said the results reinforce the need to keep ocular rosacea in mind when examining a patient.

“The study is a reminder that ocular rosacea is, like its facial counterpart, an inflammatory disease that can manifest in many ways; for this reason, it’s often misdiagnosed or missed altogether,” Dr. Williams told this news organization. “This is unfortunate because it is usually easily managed.”

She added that there is a need for more randomized, controlled studies to determine optimal treatments for ocular rosacea, which is underdiagnosed. Part of the reason she believes it is underdiagnosed is that often “ophthalmologists don’t think about ocular rosacea specifically, unless they are given the information that the patient suffers from rosacea. The patient may not be aware that their skin and eye problems are connected.”

The take-home message of the study, Dr. Williams added, is that dermatologists who treat rosacea should be ready to screen their patients with rosacea for ocular symptoms, as well as have a basic understanding of ocular rosacea and know when to refer patients to an ophthalmologist.

“Preservative-free eye drops are usually well tolerated and a good starting point for those cases that are limited to symptoms only,” she said. “However, once a patient has signs of overt inflammation on exam, such as arcades of blood vessels on the eyelid margin or on the white of the eye, prescription medication is usually needed.”

A limitation of the study is that both eyes of patients were not included, said Dr. Williams, noting that ocular rosacea is usually bilateral.

Also asked to comment on the results, Marc Lupin, MD, a dermatologist in Victoria, B.C., and clinical instructor in the department of dermatology and skin science, University of British Columbia, Vancouver, noted that one of the shortcomings of the study is that it did not account for any effect of treatment.

“Were they on treatment for their rosacea either during the study or before the study?” asked Dr. Lupin. “That would affect the ocular findings.” Still, he agreed that the study underlines the need for dermatologists to be aware of the high incidence of ocular rosacea in patients and to appreciate that it can present subtly.

The study authors, Dr. Williams, and Dr. Lupin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with rosacea are more likely to experience ocular symptoms, including foreign body sensations, itching, dryness, hyperemia, and conjunctival telangiectasia, according to a study recently published in International Ophthalmology.

In the study, investigators compared the right eyes of 76 patients with acne rosacea and 113 age-matched and gender-matched patients without rosacea. The mean age of the patients was 47-48 years, and about 63% were females. Ophthalmologic examinations that included tear breakup time and optical CT-assisted infrared meibography were conducted, and participants were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire, which the authors say is widely used to assess aspects of ocular surface diseases.

National Rosacea Society

Compared with controls, significantly more patients with rosacea had itching (35.5% vs. 17.7%), dryness (46.1% vs. 10.6%), hyperemia (10.5% vs. 2.7%), conjunctival telangiectasia (26.3% vs. 1.8%), and meibomitis (52.6% vs. 31%) (P ≤ .05 for all), according to the investigators, from the departments of ophthalmology and dermatology, Dokuz Eylul University, Izmir, Turkey. The most common ocular symptom among those with rosacea was having a foreign body sensation (53.9% vs. 24.8%, P < .001).

Ocular surface problems were also more common among those with rosacea, and OSDI scores were significantly higher among those with rosacea, compared with controls.

Estee Williams, MD, a dermatologist in private practice in New York and assistant clinical professor of dermatology at Mount Sinai Hospital, also in New York, who was not involved with the study, said the results reinforce the need to keep ocular rosacea in mind when examining a patient.

“The study is a reminder that ocular rosacea is, like its facial counterpart, an inflammatory disease that can manifest in many ways; for this reason, it’s often misdiagnosed or missed altogether,” Dr. Williams told this news organization. “This is unfortunate because it is usually easily managed.”

She added that there is a need for more randomized, controlled studies to determine optimal treatments for ocular rosacea, which is underdiagnosed. Part of the reason she believes it is underdiagnosed is that often “ophthalmologists don’t think about ocular rosacea specifically, unless they are given the information that the patient suffers from rosacea. The patient may not be aware that their skin and eye problems are connected.”

The take-home message of the study, Dr. Williams added, is that dermatologists who treat rosacea should be ready to screen their patients with rosacea for ocular symptoms, as well as have a basic understanding of ocular rosacea and know when to refer patients to an ophthalmologist.

“Preservative-free eye drops are usually well tolerated and a good starting point for those cases that are limited to symptoms only,” she said. “However, once a patient has signs of overt inflammation on exam, such as arcades of blood vessels on the eyelid margin or on the white of the eye, prescription medication is usually needed.”

A limitation of the study is that both eyes of patients were not included, said Dr. Williams, noting that ocular rosacea is usually bilateral.

Also asked to comment on the results, Marc Lupin, MD, a dermatologist in Victoria, B.C., and clinical instructor in the department of dermatology and skin science, University of British Columbia, Vancouver, noted that one of the shortcomings of the study is that it did not account for any effect of treatment.

“Were they on treatment for their rosacea either during the study or before the study?” asked Dr. Lupin. “That would affect the ocular findings.” Still, he agreed that the study underlines the need for dermatologists to be aware of the high incidence of ocular rosacea in patients and to appreciate that it can present subtly.

The study authors, Dr. Williams, and Dr. Lupin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with rosacea are more likely to experience ocular symptoms, including foreign body sensations, itching, dryness, hyperemia, and conjunctival telangiectasia, according to a study recently published in International Ophthalmology.

In the study, investigators compared the right eyes of 76 patients with acne rosacea and 113 age-matched and gender-matched patients without rosacea. The mean age of the patients was 47-48 years, and about 63% were females. Ophthalmologic examinations that included tear breakup time and optical CT-assisted infrared meibography were conducted, and participants were asked to complete the Ocular Surface Disease Index (OSDI) questionnaire, which the authors say is widely used to assess aspects of ocular surface diseases.

National Rosacea Society

Compared with controls, significantly more patients with rosacea had itching (35.5% vs. 17.7%), dryness (46.1% vs. 10.6%), hyperemia (10.5% vs. 2.7%), conjunctival telangiectasia (26.3% vs. 1.8%), and meibomitis (52.6% vs. 31%) (P ≤ .05 for all), according to the investigators, from the departments of ophthalmology and dermatology, Dokuz Eylul University, Izmir, Turkey. The most common ocular symptom among those with rosacea was having a foreign body sensation (53.9% vs. 24.8%, P < .001).

Ocular surface problems were also more common among those with rosacea, and OSDI scores were significantly higher among those with rosacea, compared with controls.

Estee Williams, MD, a dermatologist in private practice in New York and assistant clinical professor of dermatology at Mount Sinai Hospital, also in New York, who was not involved with the study, said the results reinforce the need to keep ocular rosacea in mind when examining a patient.

“The study is a reminder that ocular rosacea is, like its facial counterpart, an inflammatory disease that can manifest in many ways; for this reason, it’s often misdiagnosed or missed altogether,” Dr. Williams told this news organization. “This is unfortunate because it is usually easily managed.”

She added that there is a need for more randomized, controlled studies to determine optimal treatments for ocular rosacea, which is underdiagnosed. Part of the reason she believes it is underdiagnosed is that often “ophthalmologists don’t think about ocular rosacea specifically, unless they are given the information that the patient suffers from rosacea. The patient may not be aware that their skin and eye problems are connected.”

The take-home message of the study, Dr. Williams added, is that dermatologists who treat rosacea should be ready to screen their patients with rosacea for ocular symptoms, as well as have a basic understanding of ocular rosacea and know when to refer patients to an ophthalmologist.

“Preservative-free eye drops are usually well tolerated and a good starting point for those cases that are limited to symptoms only,” she said. “However, once a patient has signs of overt inflammation on exam, such as arcades of blood vessels on the eyelid margin or on the white of the eye, prescription medication is usually needed.”

A limitation of the study is that both eyes of patients were not included, said Dr. Williams, noting that ocular rosacea is usually bilateral.

Also asked to comment on the results, Marc Lupin, MD, a dermatologist in Victoria, B.C., and clinical instructor in the department of dermatology and skin science, University of British Columbia, Vancouver, noted that one of the shortcomings of the study is that it did not account for any effect of treatment.

“Were they on treatment for their rosacea either during the study or before the study?” asked Dr. Lupin. “That would affect the ocular findings.” Still, he agreed that the study underlines the need for dermatologists to be aware of the high incidence of ocular rosacea in patients and to appreciate that it can present subtly.

The study authors, Dr. Williams, and Dr. Lupin disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lipedema – a disease that causes excess fat to accumulate primarily in the lower part of the body – is a condition “that most physicians in the U.S. don’t understand,” according to C. William Hanke, MD, MPH.

“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.

“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”

Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.

Courtesy Dr. C. William Hanke.

Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”

One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
 

Lipedema stages, treatment

Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.

“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”

In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.

In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”

A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.

Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.

“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”

Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.

Dr. Hanke reported having no financial conflicts related to his presentation.
 

Lipedema – a disease that causes excess fat to accumulate primarily in the lower part of the body – is a condition “that most physicians in the U.S. don’t understand,” according to C. William Hanke, MD, MPH.

“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.

“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”

Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.

Courtesy Dr. C. William Hanke.

Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”

One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
 

Lipedema stages, treatment

Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.

“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”

In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.

In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”

A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.

Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.

“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”

Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.

Dr. Hanke reported having no financial conflicts related to his presentation.
 

Lipedema – a disease that causes excess fat to accumulate primarily in the lower part of the body – is a condition “that most physicians in the U.S. don’t understand,” according to C. William Hanke, MD, MPH.

“This disease is well known in Europe, especially in the Netherlands, Germany, and Austria, but in this country, I believe most dermatologists have never heard of it,” Dr. Hanke said at the ODAC Dermatology, Aesthetic & Surgical Conference.

Clinically, patients with lipedema – also known as “two-body syndrome” – present with a symmetric, bilateral increase in subcutaneous fat, with “cuffs of fat” around the ankles. It usually affects the legs and thighs; the hands and feet are not affected.

“From the waist on up, the body looks like one person, and from the waist on down, it looks like an entirely different person,” said Dr. Hanke, a dermatologist who is program director for the micrographic surgery and dermatologic oncology fellowship training program at Ascension St. Vincent Hospital in Indianapolis. “Just think of the difficulty that the person has with their life in terms of buying clothes or social interactions. This is a devastating problem.”

Lipedema almost always affects women and is progressive from puberty. “Characteristically, patients have pain and bruise easily in the areas of lipedema,” said Dr. Hanke, who has served as president of the American Academy of Dermatology, the American Society for Dermatologic Surgery, the American College of Mohs Surgery, and the International Society for Dermatologic Surgery. The affected areas are painful to touch, making exercise uncomfortable for patients, he said.

Courtesy Dr. C. William Hanke.

Lipedema can be masked by obesity, “so, if you superimpose generalized obesity on lipedema, you have an even more difficult problem,” he added. “A physician who doesn’t understand the disease may perform standard nontumescent liposuction under general anesthesia, with cannulas, which traumatize lipedematous fat. Thereby, a patient with lipedema can then be inadvertently transformed into a patient with lympholipedema. Then you’ve got even an even worse problem.”

One might think that the rate of diabetes would be high among lipedema patients, “but diabetes is essentially nonexistent in this group,” he continued. However, patients with lipedema “may develop hypothyroidism, venous disease, joint pain, and fibrosis in the fat as the disease progresses.”
 

Lipedema stages, treatment

Lipedema is defined by three clinical stages: Stage one is characterized by an enlarged subcutaneous fat department, but the skin surface is smooth. In stage 2, the skin surface becomes wavy with irregularities and dents, and in stage 3, patients develop large deforming nodules and hanging flaps.

“If we can diagnose lipedema in the early stages and perform tumescent liposuction using tumescent local anesthesia, we can prevent the progression of the disease,” Dr. Hanke said. For patients who meet criteria for tumescent liposuction, three to six treatments may be required for stage 3 disease. “Tumescent local anesthesia should be used, because liposuction using tumescent local anesthesia is atraumatic to fat,” he said. “Usually, the most painful areas are treated first.”

In a single-center study from Germany that followed 85 patients who underwent tumescent liposuction for lipedema, researchers found that improvements in pain, bruising, and mobility were sustained at 4 and 8 years following the procedure. Patient quality of life and cosmetic appearance were also sustained.

In terms of liposuction’s cosmetic effects, “the goal of liposuction in lipedema patients is different,” Dr. Hanke said. “The goal is to get these people moving again, stabilize their weight, and minimize progression of the disease. Cosmetic improvement is secondary.”

A more recent follow-up study of 60 patients from the same single-center German study showed that the positive effects of liposuction lasted 12 years postoperatively without relevant progression of disease.

Following the first International Consensus Conference on Lipedema in Vienna in 2017, Dr. Hanke and colleagues published guidelines on preventing progression of lipedema with liposuction using tumescent local anesthesia.

“If patients with lipedema gain weight, the problem becomes even worse,” he said. “A sensible diet and nontraumatic exercise like water aerobics is ideal. If patients pursue yo-yo dieting, more and more fat stays in the legs after each cycle. Sometimes I’ll refer overweight patients with lipedema for a bariatric surgery consult.”

Dr. Hanke noted that Karen Herbst, MD, PhD, an endocrinologist at the University of Arizona, Tucson, who is widely considered an expert on the medical management of lipedema, has a website on lipedema care.

Dr. Hanke reported having no financial conflicts related to his presentation.
 

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

To the Editor:

A 44-year-old man with a history of systemic lupus erythematosus (SLE) complicated by lupus nephritis, end-stage renal disease, and antiphospholipid syndrome was evaluated for progressive skin tightening over the last 3 years, predominantly on the hands but also involving the feet, legs, and arms. Physical examination revealed multiple flesh-colored to hypopigmented, bound-down, indurated, fissured plaques over the distal upper and lower extremities, most prominent over the hands (Figure 1). Yellow plaques appeared on the lateral sclera of both eyes (Figure 2). A diagnosis of nephrogenic systemic fibrosis (NSF) was supported by typical findings on punch biopsy, including a proliferation of dermal fibroblasts with thickened collagen bundles and mucin deposition.

Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, is characterized by fibrotic plaques and nodules that tend to be bilateral.¹ The chronic course of this disease often is accompanied by flexion contractures. Yellow scleral plaques caused by calcium phosphate deposition are present in up to 75% of cases and are more specific to a diagnosis of NSF in patients younger than 45 years.^1,2 A strong association exists between NSF and gadolinium contrast agents in patients with acute renal failure; our patient later confirmed multiple gadolinium exposures years prior. Deposits of gadolinium have even been found in NSF skin lesions.²

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

Most practitioners recommend a host of non-medical therapeutic options to their patients with migraine. The best studied and safest, most effective supplements remain magnesium, riboflavin/B₂, and CoQ10. Alpha-lipoic acid (ALA) is a supplement with both antioxidant and anti-inflammatory effects that has showed positive protective effects in a number of medical conditions, including diabetes and episodes of oxidative stress. One migraine study¹ evaluated serum ALA levels and found over 90% of people with migraine to deficient. This study sought to observe the potential benefit of supplementation with ALA in patients with episodic migraine.

This was a randomized, double-blind placebo-controlled trial over the course of 3 months. In this study, 92 female subjects with episodic migraine (defined as experiencing >2 but <15 days of headache per month) were recruited and randomized to receiving 300 mg ALA twice daily or placebo. Patients with chronic migraine, in menopause, pregnant, or lactating were excluded, as were patients with the presence of other chronic medical issues, or patients who had taken antioxidant supplements in the previous 4 months.

The primary outcomes of migraine severity, frequency, and Headache Impact Test (HIT-6) score were found to be significantly improved in the intervention group; duration of headache was not significantly different. Biochemical analysis of the two groups did show a difference in the lactate level of the intervention group, and this was considered a secondary outcome. Relevant side effects were primarily gastrointestinal, including stomach pain (higher in the placebo group), increased appetite, and constipation.

There is a great interest in finding effective non-medical treatments for migraine. These are frequently used as an adjunct to other preventive medications, or potentially as a stand-alone treatment for low frequency migraine. Many patients prefer non-medical options as well, and unfortunately many of the treatments they read about online or in less scientific spaces are unproven or unsafe. Supplementation remains an important part of migraine treatment for many practitioners and patients.

This study argues that ALA can be considered a safe and effective treatment for episodic migraine. When patients ask about non-medical options, ALA can be an additional treatment worth considering. Many patients are already taking multiple supplements before seeing their specialist, and this article  informs us that there may be some treatment benefit for this supplement as well. We may not be recommending this supplement alone as a preventive treatment for migraine, but we can add a new non-medical option to consider to our mix.

Using preventive medication in pediatrics is now more controversial than it had been previously. The well known The Childhood and Adolescent Migraine Prevention (CHAMP) trial² surprised many in the field by revealing that were no significant differences in headache frequency or disability when comparing children with migraine who received preventive medications or placebo. The CHAMP trial spotlighted the effect of non-medical therapies (cognitive behavioral therapy, biofeedback) and education. Many pediatric specialists have altered their practice paradigm in response to these results and have been more reticent to prescribe preventive medications for children with migraine. This is due to concern for potential side effects in light of the absence of direct benefit.

In an observational study of pediatric migraine,³ the investigators followed 186 children with migraine over a 3-year period to determine if the use of a number of preventive medications addresses disability (measured by Pediatric Migraine Disability Assessment [PedMIDAS]) as well as frequency, severity and duration of migraine. Other bothersome features of migraine were followed including the presence of nausea, vomiting, photophobia, analgesic use, and the side effects of the preventive medication.

The preventive medications used were cyproheptadine, flunarazine, propranolol, and topiramate—all at weight based doses. It is important to note that amitriptyline was not used in the study and there was no placebo group. This was a Turkish population, the median age was 14, and 63% were female, all of which are appropriate for a pediatric migraine study. Treatment efficacy was defined as a 50% reduction of symptoms. This was achieved in 90% of subjects in the topiramate group, 75% in the propranolol group, and 52-53% in the flunarazine and cyproheptadine groups.

Medication side effects were divided into minor or significant side effects. The only significant side effect noted was 3% of patient with palpitations; minor side effects were changes in appetite and drowsiness. More than half (57%) of patients taking topiramate experienced some side effect, 51% of the cyproheptadine group did as well, and the propranolol and flunarazine groups were noted to have side effects in 22% and 13%, respectively. Overall, 31.7% of patients had some side effect.  

PedMIDAS scores improved significantly with the use of preventive medications; migraine frequency improved significantly as well, especially in the topiramate group. This study argues for the use of preventive medications in pediatric migraine. One of the most commonly used medications for migraine prevention was not investigated unfortunately. Amitriptyline is widely considered a safe and effective migraine prophylactic medication, especially at low doses. One important takeaway is the frequency of side effects at all, and especially with topiramate. It is unclear how many patients stopped their preventive medications due to a side effect. In light of this study, propranolol, which is often overlooked, might be considered a better choice for children with migraine.

Most of the patients with migraine we see are in their most productive years. Migraine disability can be a major difficulty for our patients, especially as it relates to work. The American Migraine Foundation and American Headache Society have both recently taken on initiatives that relate to migraine in the workplace. Migraine epidemiologic studies have shown that people with migraine are more likely to experience a negative impact on their careers, and migraine disability scores weigh time absent from work as well as lower function at work. Many people with migraine are concerned that having migraine may hold them back from being hired or achieving promotion.

Autio et al performed a retrospective analysis of occupationally active patients treated at a single provider (the Finnish health clinic Terveystalo).⁴ The authors first looked for erenumab responders, who they defined as patients who received two prescriptions for erenumab and no other calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) medication. These patients were followed for 12 months, and their data was compared to the 12-month period prior to initiating erenumab. The authors evaluated headache-related sick days, all-cause sick days, healthcare visits, and prescriptions for all medications based on a registry. This registry also provided an age- and sex-matched control group of patients with migraine not taking any CGRP mAb medication.

A total of 162 patients were included, 82 in the erenumab responder group.  Headache-related sick days decreased by 74%, and headache-related healthcare visits decreased by 44%. Triptan prescription use decreased by 31.5%; all-cause sick days and healthcare visits differences were not statistically significant.

Prevention remains key in improving our patients’ quality of life and a large factor in this is their work life. This study shows that intervention with erenumab significantly decreases migraine-related absenteeism. It could be argued that the other CGRP mAb medications may have the same effect, as can many other preventive therapies. It can also be argued that even with this data we can only assume that patients function better at work with preventive therapies. Further studies will also look at the degree that “presenteeism” plays in the workplace—people who show up to work but are functioning at a lesser extent due to migraine. That said, this is an important step towards recognizing the burden migraine disability has on our patients’ work life, and the extent that prevention can improve their quality of life.

References

1. Kelishadi MR et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep. 2022;12:271 (Jan 7).
2. Powers SW et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl  J Med. 2017;376(2):115-124. Doi: 10.1056/NEJMoa1610384.
3. Tekin H, Edem P. Effects and side effects of migraine prophylaxis in children. Pediatr Int. 2021 (Dec 14).

1. Autio H et al. Erenumab decreases headache-related sick leave days and health care visits: a retrospective real-world study in working patients with migraine. Neurol Ther. 2021 (Dec 10).

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

A version of this article first appeared on Medscape.com.

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

A version of this article first appeared on Medscape.com.

All else being equal, I’d prefer to do nothing. Whether this is nihilism, laziness, or experience is a matter of debate. The American College of Chest Physicians (CHEST) Guidelines on therapy for venous thromboembolism (VTE) opened a door for withholding treatment for isolated subsegmental pulmonary embolism (ISSPE) in 2016 and kept it open in 2021. I was happy to walk through it and withhold therapy if it wasn’t indicated.

ISSPE is truly a conundrum. With advances in technology, the distal vessels in the lung became visible on commercial CT a little more than 10 years ago. The subsegmental branches are located after the fourth bifurcation of the pulmonary arterial system, and the new technology offered resolution adequate to identify clot in these vessels. But the new technology told us nothing about how to manage clot isolated to the subsegmental vasculature.

Autopsy data say clot in these vessels is common, even in patients who were never diagnosed with VTE while they were alive. To some degree then, the pulmonary arterial system is thought to serve as a filter to prevent clot from crossing to the systemic circulation and causing stroke. This led some to speculate that the subsegmental pulmonary arteries are supposed to contain clot and that we simply couldn’t see it before now. If this theory is correct, the practice of providing anticoagulation for ISSPE could increase bleeding without reducing the risk for VTE recurrence.

Management studies generally supported this concept. In 2007, a trial that was published in JAMA randomized patients to two different diagnostic strategies: ventilation-perfusion (VQ) and CT. CT detected more clot than VQ did, so more anticoagulation was given in the CT arm. Yet, the VTE rate during follow-up was not significantly different between arms. The implication? Some of the clots detected by CT were of lesser clinical significance and didn’t need to be treated.

Meta-analytic data from management trials also suggested that some pulmonary emboli (PE) need not be treated. Data also show when compared with patients who have more proximal PE, those with ISSPE have lower pretest probability for VTE, are less symptomatic, and have a lower burden of coexistent lower extremity thrombosis (deep vein thrombosis [DVT]).

In response to this data, the CHEST Guidelines began cautiously providing the option for withholding therapy in patients who were diagnosed with ISSPE in 2016. Their recommendations stated that patients should be stratified for recurrence risk and have lower extremity ultrasonography performed to rule out DVT. A patient with ISSPE, a low recurrence risk, and a negative ultrasound can have anticoagulation withheld. This made perfect sense to me based on what I thought I knew at the time.

Recently published data cast doubt on my nihilism. The first prospective study designed specifically to assess the safety of withholding therapy for ISSPE suggests that this practice could be dangerous. How did this happen? The trial was very well done, and the authors enrolled the right population. All of the patients had ISSPE, low recurrence risk, and negative lower extremity ultrasound. The authors were anticipating a 1% VTE rate at 90 days based on prior data but instead found a rate of 3.1% (1.6%-6.1%). They point out that this rate is not different from those seen in patients with more proximal PE who are treated with anticoagulation. However, they acknowledge that it is higher than what’s considered acceptable and warrants therapeutic anticoagulation.

So what should we do now? We treat ISSPE, that’s what. All the arguments for withholding therapy remain valid, the recurrence rate is reasonably low, and none of the recurrent VTEs in the new study were fatal. There’s still no doubt that some patients with PE won’t benefit from anticoagulation. Unfortunately, we currently lack the tools to identify them. The risk-benefit ratio for recurrence versus bleeding will be tighter with ISSPE, particularly when there’s only one clot. Unless the bleeding risk is elevated though, the ratio still favors treatment.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center.

A version of this article first appeared on Medscape.com.

COVID-19 vaccine hesitancy may be associated with traumatic events in childhood that undermine trust, including domestic violence, substance abuse in the home, or neglect, data published Feb. 1 suggest.

The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.

The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.

The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.

For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.

Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.

However, he said, the association they found may have key messages for clinicians.

“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
 

More trauma, less trust

The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.

The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.

It also included personal details and long-term health information.

About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.

According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.

They also investigated measures of trust and preference for different health regulations.

People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.

“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.

People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.

People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions. 

“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.

He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.

It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
 

Loss of control

“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.

She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.

Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.

Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.

She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
 

Young adults of particular concern

The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.

The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.

“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”

This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COVID-19 vaccine hesitancy may be associated with traumatic events in childhood that undermine trust, including domestic violence, substance abuse in the home, or neglect, data published Feb. 1 suggest.

The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.

The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.

The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.

For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.

Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.

However, he said, the association they found may have key messages for clinicians.

“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
 

More trauma, less trust

The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.

The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.

It also included personal details and long-term health information.

About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.

According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.

They also investigated measures of trust and preference for different health regulations.

People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.

“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.

People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.

People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions. 

“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.

He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.

It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
 

Loss of control

“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.

She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.

Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.

Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.

She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
 

Young adults of particular concern

The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.

The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.

“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”

This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

COVID-19 vaccine hesitancy may be associated with traumatic events in childhood that undermine trust, including domestic violence, substance abuse in the home, or neglect, data published Feb. 1 suggest.

The findings by Mark A. Bellis, DSc, College of Human Sciences, Bangor (Wales) University, and colleagues were published online in BMJ Open.

The results are especially significant, the authors say, because of the prevalence of adverse childhood experiences (ACEs) globally, with proportions of people having multiple traumas in some countries at 10% or more of the population.

The authors wrote that hesitancy or refusal to get the vaccine increased with the number of traumas reported.

For example, hesitancy was three times higher among people who had experienced four or more types of childhood trauma than among those who did not report any traumatic events.

Dr. Bellis told this news organization that though their work suggests that higher levels of ACEs are linked with higher vaccine hesitancy, it is by no means the only reason people choose not to get vaccinated.

However, he said, the association they found may have key messages for clinicians.

“For clinicians, simply being trauma informed can help,” Dr. Bellis said. “Understanding how such childhood adversity can affect people may help them when discussing vaccines, and in understanding resistance to what is a complex medical issue and one that requires considerable trust. What can appear routine to a clinician may be a difficult leap of faith especially for those who have poorer experiences of trusting even within family settings.”
 

More trauma, less trust

The authors used responses to a nationally representative telephone survey of adults in Wales taken between December 2020 and March 2021, when COVID-19 restrictions were in force. Out of 6,763 people contacted, 2,285 met all criteria and answered all the questions and were included in the final analysis.

The survey asked about nine types of ACEs before the age of 18, including: parental separation; physical, verbal, and sexual abuse; exposure to domestic violence; and living with a household member who has mental illness, misuses alcohol and/or drugs, or who was incarcerated.

It also included personal details and long-term health information.

About half of the respondents said they hadn’t experienced any childhood trauma. Of those who did, one in five said they had experienced one type, 17% reported two to three types, and 10% reported four or more.

According to the authors, prevalence of ACEs reported was consistent with other comparable population surveys, including those conducted face to face.

They also investigated measures of trust and preference for different health regulations.

People with more ACEs were more likely to have low trust in National Health Service COVID-19 information.

“Other sociodemographics and a history of either chronic disease or COVID-19 infection were not significantly associated with low trust,” the authors pointed out.

People reporting higher ACEs also were more likely to report that they felt they were unfairly restricted by the government. People with four or more ACEs were twice as likely than were those with no ACEs to say they felt unfairly restricted and wanted rules such as mandatory masking to stop.

People with four or more types of trauma were almost twice as likely to ignore the restrictions as were those who hadn’t experienced any – 38% versus 21% – to ignore the restrictions, even after the researchers accounted for associations with sociodemographic factors and previous COVID-19 infection or a history of long-term conditions. 

“Clinicians can be a powerful voice to counter more alarmist or even conspiratorial messages that might otherwise resonate with those who find trust difficult,” Dr. Bellis said.

He said that the effect of childhood adversity needs to be considered at all levels in health systems. Overarching public health strategists should include ways to earn trust to counter resistance in some of the most vulnerable communities where ACEs can be higher.

It will also be important in the short-term to “provide reassurance, build community champions, and understand the low base from which trust needs to be built,” he said.
 

Loss of control

“Past traumatic experiences can predispose someone to avoid things that remind them of that trauma. This avoidance protects them from re-experiencing the negative symptoms and behaviors that come with it. Whether this results into hesitancy of something that would benefit their health is not well known,” Consuelo Cagande, MD, senior associate program director and fellowship adviser in the department of child and adolescent psychiatry and behavioral sciences, Children’s Hospital of Philadelphia, told this news organization.

She pointed out a limitation the authors mention that is common when using ACEs as a measure linking to future negative behaviors – that people self-report them and may misremember or misreport them.

Another limitation is the potential for self-selection bias, as participation level was 36.4%, though the authors noted that is not unusual for unsolicited telephone surveys.

Dr. Cagande said that fearing loss of control may be another factor at play in having to follow restrictions, such as quarantining and masking, social distancing, or mandated vaccinations.

She said it’s important to understand a person’s reason for hesitancy to vaccines and work with the person with the help of the community, to help them trust and feel safe.
 

Young adults of particular concern

The 18- to 29-year-old age group is of particular concern, Dr. Bellis said.

The researchers estimated the likely rates of vaccine hesitancy according to childhood trauma and age, and the numbers ranged from around 3.5% among those aged 70 and older with no experience of childhood adversity to 38% among 18- to 29-year-olds who had experienced four or more types of childhood trauma.

“Childhood adversity can be an especially raw issue in this group,” he explained. “Some have already been obliged to sacrifice substantial proportions of their teenage lives and some will have suffered greater exposure to adverse childhood experiences as a result of being isolated during the pandemic, sometimes in difficult home environments. Our results suggest that this age group and especially those with high levels of ACEs are some of the most likely to be vaccine hesitant.”

This work was supported by Public Health Wales. The study authors and Dr. Cagande reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.